Lörincz Attila T, Richart Ralph M
Digene Corporation, Gaithersburg, Md 20878, USA.
Arch Pathol Lab Med. 2003 Aug;127(8):959-68. doi: 10.5858/2003-127-959-HPDTAA.
Our objective was to review current large studies of human papillomavirus (HPV) DNA testing as an adjunct to the Papanicolaou test for cervical cancer screening programs. We analyzed 10 large screening studies that used the Hybrid Capture 2 test and 3 studies that used the polymerase chain reaction test in a manner that enabled reliable estimates of accuracy for detecting or predicting high-grade cervical intraepithelial neoplasia (CIN). Most studies allowed comparison of HPV DNA and Papanicolaou testing and estimates of the performance of Papanicolaou and HPV DNA as combined tests. The studies were selected on the basis of a sufficient number of cases of high-grade CIN and cancer to provide meaningful statistical values. Investigators had to demonstrate the ability to generate reasonably reliable Hybrid Capture 2 or polymerase chain reaction data that were either minimally biased by nature of study design or that permitted analytical techniques for addressing issues of study bias to be applied. Studies had to provide data for the calculation of test sensitivity, specificity, predictive values, odds ratios, relative risks, confidence intervals, and other relevant measures. Final data were abstracted directly from published articles or estimated from descriptive statistics presented in the articles. In some studies, new analyses were performed from raw data supplied by the principal investigators. We concluded that HPV DNA testing was a more sensitive indicator for prevalent high-grade CIN than either conventional or liquid cytology. A combination of HPV DNA and Papanicolaou testing had almost 100% sensitivity and negative predictive value. The specificity of the combined tests was slightly lower than the specificity of the Papanicolaou test alone, but this decrease could potentially be offset by greater protection from neoplastic progression and cost savings available from extended screening intervals. One "double-negative" HPV DNA and Papanicolaou test indicated better prognostic assurance against risk of future CIN 3 than 3 subsequent negative conventional Papanicolaou tests and may safely allow 3-year screening intervals for such low-risk women.
我们的目的是回顾当前将人乳头瘤病毒（HPV）DNA检测作为巴氏试验辅助手段用于宫颈癌筛查项目的大型研究。我们分析了10项使用杂交捕获2检测法的大型筛查研究以及3项使用聚合酶链反应检测法的研究，其分析方式能够可靠地估计检测或预测高级别宫颈上皮内瘤变（CIN）的准确性。大多数研究允许对HPV DNA检测和巴氏试验进行比较，并估计巴氏试验和HPV DNA联合检测的性能。这些研究是基于足够数量的高级别CIN和癌症病例来选择的，以提供有意义的统计值。研究人员必须证明有能力生成合理可靠的杂交捕获2或聚合酶链反应数据，这些数据要么受研究设计性质的偏差影响最小，要么允许应用解决研究偏差问题的分析技术。研究必须提供用于计算检测敏感性、特异性、预测值、比值比、相对风险、置信区间及其他相关指标的数据。最终数据直接从已发表的文章中提取，或根据文章中呈现的描述性统计数据估算。在一些研究中，根据主要研究者提供的原始数据进行了新的分析。我们得出结论，对于普遍存在的高级别CIN，HPV DNA检测比传统或液基细胞学检测更敏感。HPV DNA检测和巴氏试验联合使用的敏感性和阴性预测值几乎达到100%。联合检测的特异性略低于单独巴氏试验的特异性，但这种降低可能会被因肿瘤进展风险降低以及延长筛查间隔带来的成本节约所抵消。一次HPV DNA检测和巴氏试验均为阴性，相较于随后3次传统巴氏试验阴性，对未来CIN 3风险具有更好的预后保证，对于此类低风险女性可安全地允许3年的筛查间隔。
